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https://www.readbyqxmd.com/read/27668757/mountain-cultivated-ginseng-attenuates-phencyclidine-induced-abnormal-behaviors-in-mice-by-positive-modulation-of-glutathione-in-the-prefrontal-cortex-of-mice
#1
The-Vinh Tran, Eun-Joo Shin, Sung Kwon Ko, Yunsung Nam, Yoon Hee Chung, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kiyofumi Yamada, Toshitaka Nabeshima, Jae Kyung Byun, Hyoung-Chun Kim
Escalating evidence indicates that ginseng treatment protects against psychotoxic behaviors and memory impairment. Although the underlying mechanism of schizophrenia remains elusive, recent investigations proposed that downregulation of glutathione (GSH) can be involved in the pathogenesis of this disorder. Since little is known about the effects of ginseng in a schizophrenia-like animal model, we selected mountain-cultivated ginseng (MG) from a variety of ginseng extracts to investigate the effect of ginseng on the psychosis induced by phencyclidine (PCP) in mice...
September 26, 2016: Journal of Medicinal Food
https://www.readbyqxmd.com/read/27529801/subchronic-administration-of-phencyclidine-produces-hypermethylation-in-the-parvalbumin-gene-promoter-in-rat-brain
#2
Helene A Fachim, Umarat Srisawat, Caroline F Dalton, Michael K Harte, Samuel Marsh, Joanna C Neill, Gavin P Reynolds
AIM: A deficit in parvalbumin neurons is found in schizophrenia and several animal models of the disease. In this preliminary study, we determined whether one such model, phencyclidine (PCP) administration, results in changes in DNA methylation in the rat Pvalb promoter. MATERIALS & METHODS: DNA from hippocampus and prefrontal cortex from rats, which 6 weeks previously received either 2 mg/kg PCP or vehicle for 7 days, underwent bisulphite pyrosequencing to determine methylation...
September 2016: Epigenomics
https://www.readbyqxmd.com/read/27459658/factors-influencing-the-use-of-second-generation-antipsychotics-in-children-with-psychosis
#3
Sujith Ramachandran, Benjamin F Banahan, John P Bentley, Donna S West-Strum, Amit S Patel
BACKGROUND: In 2011, the U.S. Department of Health and Human Services sent a letter to state Medicaid directors explaining the need for oversight of psychiatric prescriptions for children with mental health disorders. The National Committee for Quality Alliance proposed 3 quality measures for rating managed care organizations (MCOs) that involve use of second-generation or atypical antipsychotics in children. In order to ensure appropriate use and to effectively manage the use of second-generation antipsychotics in children, MCOs need to better understand the factors that influence medication treatment decisions for children...
August 2016: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/27335180/proteomic-systems-evaluation-of-the-molecular-validity-of-preclinical-psychosis-models-compared-to-schizophrenia-brain-pathology
#4
David A Cox, Michael G Gottschalk, Hendrik Wesseling, Agnes Ernst, Jason D Cooper, Sabine Bahn
Pharmacological and genetic rodent models of schizophrenia play an important role in the drug discovery pipeline, but quantifying the molecular similarity of such models with the underlying human pathophysiology has proved difficult. We developed a novel systems biology methodology for the direct comparison of anterior prefrontal cortex tissue from four established glutamatergic rodent models and schizophrenia patients, enabling the evaluation of which model displays the greatest similarity to schizophrenia across different pathophysiological characteristics of the disease...
June 19, 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/26972135/phencyclidine-excitatory-amino-acids-psychiatry-and-drug-abuse-historical-perspectives-on-clinical-laboratory-interactions
#5
S R Zukin
Some 40 years ago phencyclidine (PCP) was developed as the prototype of a proposed new class of 'dissociative' general anesthetics, so called because it induced a marked dissociation from the environment without complete loss of consciousness. In the earliest clinical trials of PCP anesthesia, it was observed that as many as half the subjects experienced severe psychotic reactions during and beyond emergence. This striking clinical observation at once marked the failure of PCP as a suitable general anesthetic, and the beginning of a remarkable new era in basic and clinical neuroscience which can serve as an example of the interaction between clinical observation and basic science...
June 1997: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/26810316/discovery-of-5-aryl-1-3-dihydro-2h-imidazo-4-5-b-pyridin-2-ones-as-positive-allosteric-modulators-of-metabotropic-glutamate-subtype-2-mglu2-receptors-with-efficacy-in-a-preclinical-model-of-psychosis
#6
Mark E Layton, Alexander J Reif, Timothy J Hartingh, Kevin Rodzinak, Vadim Dudkin, Cheng Wang, Ken Arrington, Michael J Kelly, Robert M Garbaccio, Julie A O'Brien, Brian C Magliaro, Jason M Uslaner, Sarah L Huszar, Kerry L Fillgrove, Cuyue Tang, Yuhsin Kuo, Marlene A Jacobson
Optimization of a benzimidazolone template for potency and physical properties revealed 5-aryl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones as a key template on which to develop a new series of mGlu2 positive allosteric modulators (PAMs). Systematic investigation of aryl-SAR led to the identification of compound 27 as a potent and highly selective mGlu2 PAM with sufficient pharmacokinetics to advance to preclinical models of psychosis. Gratifyingly, compound 27 showed full efficacy in the PCP- and MK-801-induced hyperlocomotion assay in rats at CSF concentrations consistent with mGlu2 PAM potency...
February 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26808689/modulation-of-mglu2-receptors-but-not-pde10a-inhibition-normalizes-pharmacologically-induced-deviance-in-auditory-evoked-potentials-and-oscillations-in-conscious-rats
#7
Abdallah Ahnaou, Ria Biermans, Wilhelmus H Drinkenburg
Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics. Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP) are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing. Inhibition of phosphodiesterase (i.e. PDE10A) and activation of metabotropic glutamate receptor (mGluR2) signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential...
2016: PloS One
https://www.readbyqxmd.com/read/26702170/symptoms-at-onset-in-first-episode-schizophrenia-caregivers-perspectives
#8
Hema Tharoor, Aarthi Ganesh
BACKGROUND: Early recognition of symptoms is important in the management of psychosis. Caregivers understanding and attribution of symptoms plays a major role in treatment selection. AIM: The aim was to identify the various symptoms cluster recognized by caregivers at illness onset in first episode schizophrenia. SUBJECTS AND METHODS: In a cross-sectional study 40 key caregivers of patients with first episode of Schizophrenia (International Classification of Diseases-10) attending the outpatient services of Schizophrenia Research Foundation were recruited...
October 2015: Indian Journal of Psychological Medicine
https://www.readbyqxmd.com/read/26315507/partial-mglu%C3%A2-negative-allosteric-modulators-attenuate-cocaine-mediated-behaviors-and-lack-psychotomimetic-like-effects
#9
Robert W Gould, Russell J Amato, Michael Bubser, Max E Joffe, Michael T Nedelcovych, Analisa D Thompson, Hilary H Nickols, Johannes P Yuh, Xiaoyan Zhan, Andrew S Felts, Alice L Rodriguez, Ryan D Morrison, Frank W Byers, Jerri M Rook, John S Daniels, Colleen M Niswender, P Jeffrey Conn, Kyle A Emmitte, Craig W Lindsley, Carrie K Jones
Cocaine abuse remains a public health concern for which pharmacotherapies are largely ineffective. Comorbidities between cocaine abuse, depression, and anxiety support the development of novel treatments targeting multiple symptom clusters. Selective negative allosteric modulators (NAMs) targeting the metabotropic glutamate receptor 5 (mGlu5) subtype are currently in clinical trials for the treatment of multiple neuropsychiatric disorders and have shown promise in preclinical models of substance abuse. However, complete blockade or inverse agonist activity by some full mGlu5 NAM chemotypes demonstrated adverse effects, including psychosis in humans and psychotomimetic-like effects in animals, suggesting a narrow therapeutic window...
March 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26138155/role-of-the-nitric-oxide-donor-sodium-nitroprusside-in-the-antidepressant-effect-of-ketamine-in-mice
#10
Miriam A Vogt, Anne S Vogel, Natascha Pfeiffer, Peter Gass, Dragos Inta
Ketamine may represent an efficient alternative antidepressant with rapid therapeutic onset; however, the clinical use of ketamine is hampered by psychosis-like side-effects. Recent studies suggest that the nitric oxide (NO) donor sodium nitroprusside (SNP) prevents psychosis-like abnormalities triggered by ketamine or another NMDA receptor (NMDAR) antagonist, phencyclidine (PCP) in rats. SNP was shown to elicit antipsychotic effects also in humans. Considering the tight interrelation between NMDAR activation and neuronal NO synthesis, we evaluated the effect of pre-treatment with SNP on the antidepressant action of ketamine...
October 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26107664/dietary-intake-of-sulforaphane-rich-broccoli-sprout-extracts-during-juvenile-and-adolescence-can-prevent-phencyclidine-induced-cognitive-deficits-at-adulthood
#11
Yumi Shirai, Yuko Fujita, Ryota Hashimoto, Kazutaka Ohi, Hidenaga Yamamori, Yuka Yasuda, Tamaki Ishima, Hiroyuki Suganuma, Yusuke Ushida, Masatoshi Takeda, Kenji Hashimoto
Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress...
2015: PloS One
https://www.readbyqxmd.com/read/25863433/evolution-and-synthesis-of-novel-orally-bioavailable-inhibitors-of-pde10a
#12
Douglas F Burdi, John E Campbell, Jun Wang, Sufang Zhao, Hua Zhong, Jianfeng Wei, Una Campbell, Liming Shao, Lee Herman, Patrick Koch, Philip G Jones, Michael C Hewitt
The design and synthesis of highly potent, selective orally bioavailable inhibitors of PDE10A is reported. Starting with an active compound of modest potency from a small focused screen, we were able to evolve this series to a lead molecule with high potency and selectivity versus other PDEs using structure-based design. A systematic refinement of ADME properties during lead optimization led to a lead compound with good half-life that was brain penetrant. Compound 39 was highly potent versus PDE10A (IC50=1...
May 1, 2015: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/25800714/coordinating-with-the-inner-gps
#13
REVIEW
André A Fenton
The 2014 Nobel Prize for Physiology or Medicine was awarded for the discoveries that have elucidated the components of the internal positioning system that is centered on the hippocampus and entorhinal cortex. Here I provide a less than objective discussion of the importance of these accomplishments to systems neuroscience. By identifying positioning components like place, direction, distance, borders and the like, the field is given the opportunity to have a shot at piecing together how these components are integrated into the synthetic positioning sense...
June 2015: Hippocampus
https://www.readbyqxmd.com/read/25539511/increasing-endocannabinoid-levels-in-the-ventral-pallidum-restore-aberrant-dopamine-neuron-activity-in-the-subchronic-pcp-rodent-model-of-schizophrenia
#14
David D Aguilar, Li Chen, Daniel J Lodge
BACKGROUND: Schizophrenia is a debilitating disorder that affects 1% of the US population. While the exogenous administration of cannabinoids such as tetrahydrocannabinol is reported to exacerbate psychosis in schizophrenia patients, augmenting the levels of endogenous cannabinoids has gained attention as a possible alternative therapy to schizophrenia due to clinical and preclinical observations. Thus, patients with schizophrenia demonstrate an inverse relationship between psychotic symptoms and levels of the endocannabinoid anandamide...
October 31, 2014: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/24931864/novel-psychoactive-substance-intoxication-resulting-in-attempted-murder
#15
Richard Stevenson, Laurence Tuddenham
A man in his twenties who had no previous history of violence, snorted large quantities of two substances he identified as 3-methoxyphencyclidine (3-MeO-PCP), and methylenedioxypyrovalerone (MDPV); both are recognised as novel psychoactive substances, or commonly described in the media as "legal highs". He also inhaled butane gas. He experienced vivid hallucinations and developed bizarre ideas. During this state of mind he stabbed his father multiple times and was arrested and charged with attempted murder...
July 2014: Journal of Forensic and Legal Medicine
https://www.readbyqxmd.com/read/24717386/misdiagnosis-of-bipolar-depression-in-primary-care-practices
#16
Larry Culpepper
Misdiagnosis of bipolar disorder is too frequent in primary care practices. Early diagnosis of the disease is crucial for appropriate treatment and optimal outcomes, yet patients may go years without a proper diagnosis. Misdiagnosis of unipolar depression may occur when patients with depressive symptomatology report no manic or hypomanic episodes. Furthermore, bipolar disease may begin as depression and develop into bipolar disorder. Primary care physicians can watch for several red flags in patients with depressive episodes, such as poor functioning in social and work arenas, risky behaviors, and legal issues...
March 2014: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/24620939/which-pathways-to-psychiatric-care-lead-to-earlier-treatment-and-a-shorter-duration-of-first-episode-psychosis
#17
Kamaldeep Bhui, Simone Ullrich, Jeremy W Coid
BACKGROUND: The pathways to care in a first onset psychosis are diverse and may influence the chances of early treatment and therefore the duration of untreated psychosis. We test which pathways to care are associated with a delay in receiving treatment and a longer duration of untreated psychosis (DUP). METHODS: In a population based survey, we interviewed 480 people with first episode psychosis aged 18 to 64 years over a 2-year period. Information from structured interview and case files provided DSM-IV diagnostic, clinical, and demographic information...
March 12, 2014: BMC Psychiatry
https://www.readbyqxmd.com/read/24345269/the-novel-object-recognition-test-in-rodents-in-relation-to-cognitive-impairment-in-schizophrenia
#18
REVIEW
Lakshmi Rajagopal, Bill W Massey, Mei Huang, Yoshihiro Oyamada, Herbert Y Meltzer
Novel object recognition (NOR) in rodents is analogous in some ways to human declarative (episodic) memory, one of the seven cognitive domains which are abnormal in schizophrenia. Cognitive impairment in schizophrenia (CIS) accounts for the largest proportion of the poor functional outcomes in this complex syndrome, with psychosis and negative symptoms accounting for much of the rest. Current atypical antipsychotic drugs (APDs) e.g. amisulpride, aripiprazole, clozapine, lurasidone, olanzapine and risperidone, and typical APDs as well, significantly improve some, but not all aspects of CIS, including declarative memory, but not in all patients, and rarely restore normal function...
2014: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/24132898/what-can-we-learn-about-schizophrenia-from-studying-the-human-model-drug-induced-psychosis
#19
REVIEW
Robin M Murray, Alessandra Paparelli, Paul D Morrison, Arianna Marconi, Marta Di Forti
When drug-induced psychoses were first identified in the mid-20th century, schizophrenia was considered a discrete disease with a likely genetic cause. Consequently, drug-induced psychoses were not considered central to understanding schizophrenia as they were thought to be phenocopies rather than examples of the illness secondary to a particular known cause. However, now that we know that schizophrenia is a clinical syndrome with multiple component causes, then it is clear that the drug-induced psychoses have much to teach us...
October 2013: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/23942359/a-combined-metabonomic-and-proteomic-approach-identifies-frontal-cortex-changes-in-a-chronic-phencyclidine-rat-model-in-relation-to-human-schizophrenia-brain-pathology
#20
Hendrik Wesseling, Man K Chan, T M Tsang, Agnes Ernst, Fabian Peters, Paul C Guest, Elaine Holmes, Sabine Bahn
Current schizophrenia (SCZ) treatments fail to treat the broad range of manifestations associated with this devastating disorder. Thus, new translational models that reproduce the core pathological features are urgently needed to facilitate novel drug discovery efforts. Here, we report findings from the first comprehensive label-free liquid-mass spectrometry proteomic- and proton nuclear magnetic resonance-based metabonomic profiling of the rat frontal cortex after chronic phencyclidine (PCP) intervention, which induces SCZ-like symptoms...
November 2013: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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